PAIN®最新文献

{"title":"Glucagon-like peptide-1 receptor agonist treatment is associated with lower frequency of diabetic peripheral neuropathy and neuropathic pain in type 2 diabetes.","authors":"Pietro Falco, Alessandra Di Flaviani, Eleonora Galosi, Stefania Angotti, Gianfranco De Stefano, Giuseppe Di Pietro, Giulia Di Stefano, Luca D'Onofrio, Enrico Evangelisti, Caterina Leone, Daniel Litewczuk, Lars Arendt-Nielsen, Raffaella Buzzetti, Vincenza Spallone, Andrea Truini","doi":"10.1097/j.pain.0000000000004104","DOIUrl":"10.1097/j.pain.0000000000004104","url":null,"abstract":"<p><strong>Abstract: </strong>In this cross-sectional study, we investigated the frequency of diabetic peripheral neuropathy (DPN) and DPN-related neuropathic pain (painful DPN) in 500 consecutively enrolled patients with type 2 diabetes mellitus receiving standard treatment (n = 208), sodium-glucose cotransporter-2 inhibitors (SGLT2i; n = 152), or glucagon-like peptide-1 receptor agonists (GLP-1 RAs; n = 140). DPN was assessed through neurological examination, nerve conduction study, and skin biopsy when indicated; painful DPN was diagnosed using the grading system for neuropathic pain. Neuropathy severity and pain intensity were quantified with the Toronto Clinical Neuropathy Score, Pain Numerical Rating Scale, and Neuropathic Pain Symptom Inventory. The overall frequency of DPN was 58.6%, and painful DPN occurred in 26.2% of patients. GLP-1 RA treatment was associated with a lower frequency of DPN (46.4% vs 60.6% in the standard treatment group) and painful DPN (10.1% vs 35.1% and 28.3% in the standard treatment and SGLT2i groups, respectively). After adjustment for clinical and metabolic covariates, GLP-1 RA treatment was independently associated with lower odds of DPN (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.37-0.96) and painful DPN (OR 0.32, 95% CI 0.15-0.65). Neuropathy severity and pain intensity were also lower in patients receiving GLP-1 RAs. GLP-1 RA treatment was associated with a reduced frequency and severity of both DPN and painful DPN, independent of clinical and metabolic covariates. While these findings suggest potential neuroprotective and antinociceptive effects, longitudinal studies are needed to establish causality and clarify the underlying mechanisms.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"2523-2531"},"PeriodicalIF":5.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148841155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond intensity: pain distribution shapes healthcare- and treatment-seeking beliefs in individuals with and without clinical pain.","authors":"Tom Frankenstein, Sophia Intert, Tibor M Szikszay, Michał Katra, Bernhard Elsner, Robert C Coghill, Kerstin Luedtke, Waclaw M Adamczyk","doi":"10.1097/j.pain.0000000000004127","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000004127","url":null,"abstract":"<p><strong>Abstract: </strong>Pain is commonly described in sensory terms, yet its spatial characteristics are rarely quantified. We investigated whether lay beliefs about pain distribution influence theoretical decisions to seek care and treatment preferences. In a cross-sectional survey (N = 503; 49% reporting pain), participants completed thought experiments in which both visually presented pain distribution patterns (small, moderate, or large) and pain intensity (Numerical Rating Scale scores: 2, 5, 8/10) were systematically varied. For each scenario, they rated the likelihood of (1) seeking professional help (LoSH) and (2) taking analgesic medication (LoTM) on 0 to 100 scale. Participants also completed a spatial-intensity trade-off task, in which they chose between a fixed 20% reduction in intensity and variable reductions in pain distribution (20%-80%). A reversed version contrasted a fixed 80% reduction in pain distribution with variable reductions in pain intensity. LoSH and LoTM increased significantly with greater pain distribution (P < 0.001), mirroring the gradient observed for pain intensity. In the spatial-intensity trade-off task, participants' choice followed a sigmoid-like function (P < 0.001): 1% reduction in intensity was treated as equivalent to approximately a 3% reduction in distribution, indicating a systematic valuation of pain distribution. This ratio was lower in individuals experiencing pain compared with pain-free individuals. Moreover, 61% reported that pain distribution should be routinely considered in pain management alongside intensity. Results suggest that pain distribution is not merely a trivial descriptor, but a meaningful determinant of healthcare-related decision-making beliefs. Incorporating spatial metrics into clinical assessment and research may better capture how individuals implicitly evaluate pain severity.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":"167 11","pages":"2672-2683"},"PeriodicalIF":5.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychosocial interventions for reducing pain and pain-related distress in infants, children, and adolescents undergoing cancer treatment: a systematic review and meta-analysis of randomized control trials.","authors":"Karin Plummer, Mari Takashima, Julianne Richards, Amy E Mitchell, Alexandra De Young, Anthony Herbert, Lindsay Jibb, Touchamas Thailek, Brandon Meikle, Maria McCarthy, Bronwyn Griffin","doi":"10.1097/j.pain.0000000000004095","DOIUrl":"10.1097/j.pain.0000000000004095","url":null,"abstract":"<p><strong>Prospero registration: </strong>CRD42022343066.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"2503-2522"},"PeriodicalIF":5.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alexithymia moderates brain function during suppression of negative emotions in fibromyalgia.","authors":"Amaia Aguirre de Cárcer Vidal, Nell Norman-Nott, Sylvia M Gustin, Yann Quidé","doi":"10.1097/j.pain.0000000000004109","DOIUrl":"10.1097/j.pain.0000000000004109","url":null,"abstract":"<p><strong>Abstract: </strong>Fibromyalgia is associated with altered brain function and emotion regulation difficulties. Alexithymia is common in fibromyalgia and may further affect emotion regulation in this population. This study examined the interplay of alexithymia and fibromyalgia on brain function during suppression of negative emotions. Twenty-seven female participants with fibromyalgia and 30 controls performed an emotion regulation task while undergoing functional magnetic resonance imaging. Alexithymia was assessed using the Toronto Alexithymia Scale (TAS). A series of whole-brain multiple linear regressions was performed to estimate the effects of group, alexithymia, and their interaction on activation and seed-based task-related functional connectivity. Reduced activation in the left middle frontal gyrus during negative emotion suppression, as well as reduced left amygdala-right temporo-parietal junction connectivity, increased left anterior insula-right posterior insula connectivity, and increased left anterior cingulate cortex-precuneus and inferior parietal lobule connectivity were evident in fibromyalgia. Increasing alexithymia was associated to stronger left anterior insula-inferior parietal lobule connectivity, across all groups. After significant association between the group-by-TAS interaction and right amygdala-lingual gyri connectivity, moderation analysis indicated that increasing alexithymia was associated with reduced connectivity in healthy controls but not in fibromyalgia. This study highlights disrupted integration between emotional, interoceptive, and self-referential networks as a key feature of negative emotion suppression in fibromyalgia. Alexithymia moderates these disruptions by reducing emotional clarity and increasing internal focus. Interventions enhancing interoceptive awareness, fostering emotional understanding, and strengthening cognitive regulation may help normalise neural function and improve emotional functioning, especially in individuals with elevated alexithymia.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"2582-2592"},"PeriodicalIF":5.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148875630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Momentary associations of parent psychological factors, perceived child pain, and home opioid administration for postoperative pain management.","authors":"Amanda L Stone, Andrew H Rogers, Alan Hoang, Julianna Longo, Judy Garber, Jay Werkhaven, Amy S Whigham, Stephen Bruehl","doi":"10.1097/j.pain.0000000000004093","DOIUrl":"10.1097/j.pain.0000000000004093","url":null,"abstract":"<p><strong>Abstract: </strong>Characterizing the affective processes parents experience following a child's surgery and how these processes might predict their perceptions of children's pain and postoperative medication administration is critical for refining interventions to improve children's pain management. This study evaluated concurrent and lagged associations among parent affect (pain catastrophizing, negative affect, and positive affect), perceived child pain intensity, and opioid administration in the 7 days after tonsillectomy in a sample of youth ages 7 to 12 years (n = 138). Parents of potentially eligible patients were recruited before surgery and completed electronic diaries through a smartphone application 3 times daily for 7 days after surgery. Opioid administration was evaluated in the context of routine clinical care. Patients were generally prescribed a 3-day supply of liquid oxycodone for parents to administer if pain was uncontrolled by acetaminophen and ibuprofen. Of the 138 parents who completed ≥1 diary, 90 parents reported administering an opioid during the diary period (65.2%) and were included in opioid analyses. In multilevel models, both average and momentary levels of parent affect predicted parents' perceptions of their child's pain intensity, whereas only average negative affect and momentary levels of parent affect predicted odds of opioid administration. Parent pain catastrophizing had a bidirectional relation with perceived child pain in lagged analyses, with higher parent pain catastrophizing predicting higher perceived pain intensity at subsequent timepoints and vice versa. Assessing momentary levels of parent affect may be particularly important for capturing dynamic shifts that predict escalations in children's pain and opioid administration.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"2532-2542"},"PeriodicalIF":5.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Voices in pain: coproduction, creative methods, and communicating chemotherapy-induced painful neuropathy.","authors":"Katherine J Holzer, Fiona Talkington, Kathryn R Martin, Lesley A Colvin","doi":"10.1097/j.pain.0000000000004122","DOIUrl":"10.1097/j.pain.0000000000004122","url":null,"abstract":"","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"2489-2492"},"PeriodicalIF":5.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Minor role of endogenous opioids for acute pain regulation in humans: a systematic review and meta-analysis of placebo-controlled antagonist studies.","authors":"Isabell M Meier, Martin Trøstheim, Eira N Jensen, Mathias N Roland, Guro Løseth, Marie Eikemo, Siri Leknes","doi":"10.1097/j.pain.0000000000004097","DOIUrl":"10.1097/j.pain.0000000000004097","url":null,"abstract":"<p><strong>Abstract: </strong>Endogenous opioids are widely regarded as the body's natural painkillers, lending credibility to the status of opioid medications as the gold-standard analgesics. When and how much endogenous opioids downregulate pain in humans remains unclear. To determine whether and under which conditions pharmacological opioid receptor blockade increased pain in healthy volunteers, we conducted a systematic review and meta-analysis of double-blind, randomized, placebo-controlled studies administering centrally active opioid antagonists during peripheral pain testing. Literature searches were performed in Web of Science, Scopus, PubMed, and EMBASE between October 7, 2020, and June 10, 2025. Three-level random-effects meta-regressions estimated standardized mean differences (Hedges' g) in pain intensity, tolerance, unpleasantness, and threshold between antagonist and placebo conditions. In secondary analyses, to determine under which conditions pain would be higher during mu-opioid blockade, we assessed the potential moderating role of study characteristics including pain modality, location, duration, nondrug interventions, and sample sex distributions. Sixty-seven studies were included (N = 2706). Across all pain outcomes, mu-opioid blockade was associated with slightly higher pain compared with placebo (Hedges' g [95% CI] = 0.18 [0.11, 0.25]), an increase of 2.8 points on a 0 to 100 pain intensity scale. Evidence of reporting bias suggested that the effect size was slightly overestimated. Although residual heterogeneity was substantial (I 2 = 66%), study characteristics explained little or none of this variance. The most credible evidence of endogenous opioid pain regulation was found for the placebo hypoalgesia category. Overall, the slight increase in pain sensitivity during opioid blockade in healthy volunteers indicates a minor role of endogenous opioids in human pain regulation.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"2493-2502"},"PeriodicalIF":5.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148990995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From research to practice: adapting graded sensorimotor retraining for people with chronic low back pain.","authors":"Martjie Venter, Michael Hodgins, Benedict M Wand, Matthew K Bagg, Hayley B Leake, Rodrigo R N Rizzo, Brendan Mouatt, Felicity A Braithwaite, Steven Marsh, Tasha R Stanton, G Lorimer Moseley, James H McAuley, Aidan G Cashin","doi":"10.1097/j.pain.0000000000004115","DOIUrl":"10.1097/j.pain.0000000000004115","url":null,"abstract":"<p><strong>Abstract: </strong>Low back pain is a leading cause of disability worldwide, yet translation of evidence-based interventions into clinical practice remains limited. Graded sensorimotor retraining, also known as the RESOLVE program, is a complex rehabilitation intervention for people with chronic low back pain that demonstrated clinically meaningful and sustained benefits in a sham-controlled, randomised controlled trial. This study aimed to adapt the RESOLVE program for implementation into a pragmatic clinical practice setting. We conducted a two-stage adaptation study guided by established frameworks. Stage 1 involved formation of an adaptation working group, review of evidence relevant to the RESOLVE program, qualitative interest-holder engagement, and ad hoc expert consultation. Findings from Stage 1 were used to identify core and adaptable components of the intervention and contextual determinants of implementation. Adaptations (or implementation strategies) to address the adaptable intervention components and contextual determinants were proposed to a consensus group meeting during Stage 2. During this stage, a structured consensus process finalised 8 adaptations, which target intervention content, delivery, resources, and clinician training. The adaptations focus on refining and streamlining existing components to improve fit rather than removing or introducing entire new elements. Our approach provides practical guidance for future adaptations of the RESOLVE program, and other complex treatments, for clinical implementation to ultimately improve the translation of evidence-based interventions for improved patient outcomes.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"2650-2660"},"PeriodicalIF":5.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148991021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting GPR183 to reduce peripheral sensitization: evidence from rodent and human tissue analyses.","authors":"Kyle Oberkrom, Kathryn Braden, Evelyn Li, Samay R Shah, Dragan Maric, Andrew J Mannes, Paola Pacifico, Nirupa D Jayaraj, Christopher K Arnatt, Daniela Menichella, Matthew R Sapio, Daniela Salvemini","doi":"10.1097/j.pain.0000000000004124","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000004124","url":null,"abstract":"<p><strong>Abstract: </strong>Peripheral sensitization is a key process in the development of painful inflammatory conditions, driven in part by immune-cell mediator release following tissue injury. The G protein-coupled receptor, GPR183, predominantly expressed on immune cells, regulates their migration, positioning, and mediator production. However, its role in peripheral sensitization and the specific immune cells involved remains insufficiently understood. In rats, intraplantar injection of 7α,25-dihydroxycholesterol (7α,25-OHC), the most potent endogenous GPR183 ligand, produced long-lasting nociception that was prevented by the selective GPR183 antagonist SAE-14. As GPR183 activates extracellular signal-regulated kinase signaling, which influences pain pathways including nitric oxide synthase (NOS) activity and NO formation, we used NOS inhibitors and knockout animals to test the contribution of inducible and neuronal NOS isoforms to 7α,25-OHC-induced sensitization. We found that both isoforms influence this response, independent of cyclooxygenases. In a well-characterized rat incisional injury model, GPR183 protein expression increased in injured paw tissue, and SAE-14 reversed hypersensitivity. Meta-analysis of human postsurgical skin samples similarly showed elevated GPR183 expression and transcriptional changes favoring 7α,25-OHC production after injury. We identified macrophages, Langerhans cells (LCs), and T cells as the principal GPR183-expressing cell types in human skin. Ablation of LCs and removal of mature B and T cells revealed that 7α,25-OHC-evoked hypersensitivity does not depend on these cell types, leaving GPR183+ macrophages as the most likely drivers of GPR183-induced hypersensitivity. Overall, our findings define the cellular and molecular pathways linking GPR183 to peripheral sensitization and highlight GPR183 antagonism as a promising strategy for pain management.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pain education in Brazilian medical schools: a national curriculum analysis.","authors":"Thayna Caetano Alves Silva, Felipe Maia Domingues, Daiane Lazzeri Medeiros, Ana Camila de Castro Gandolfi, Felipe J J Reis","doi":"10.1097/j.pain.0000000000004129","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000004129","url":null,"abstract":"<p><strong>Abstract: </strong>Pain is a leading cause of disability worldwide, yet undergraduate medical education remains insufficient to prepare future physicians for its assessment and management. The International Association for the Study of Pain (IASP) has proposed a competency-based curriculum framework; however, its implementation in Brazilian medical education is unclear. The aim of this study was to evaluate the availability of pain education in Brazilian medical schools and assess its alignment with the IASP Curriculum Outline on Pain for Medicine. We conducted a national cross-sectional documentary analysis of all medical schools registered in the Brazilian Ministry of Education database between May 2024 and December 2025. Institutional websites were systematically screened for publicly available curricular documentation, and data were independently extracted by 2 reviewers. Variables included the presence of pain-related content, existence of a dedicated pain course, course workload, timing within the curriculum, and type of offering. Among 447 identified schools, 277 (62.0%) provided accessible curricular information. Only 47 institutions (16.9%) offered a stand-alone pain course, and 29 had detailed syllabi for item-level analysis. Most analyzed courses were mandatory and delivered in the early years of training. Alignment with IASP competencies was incomplete across all domains, with greater coverage of neurobiological and pharmacological content and limited inclusion of pain assessment and measurement, psychosocial and behavioral management, public health, ethics, and care for special populations. Pain education in Brazil is inconsistently structured and only partially aligned with international recommendations, indicating the need of comprehensive, competency-based curricular reform.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}